Antitumor Efficacy of Reticulol from <i>Streptoverticillium</i> against the Lung Metastasis Model B16F10 Melanoma

Abstract

Reticulol was isolated from the culture broth of the strain Streptoverticillium sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity against A427, a human lung tumor cell line, and B16F10, a mouse melanoma cell line. In the trypan blue staining assay for B16F10 cells, the cell viability by reticulol treatment was significantly decreased in a dose-dependent manner. The in vivo assay for the lung metastasis-blocking effect showed that reticulol injected intravenously suppressed the increase in colonies on the lung in a dose-dependent manner. In addition, the survival rate of tumor-implanted mice treated with reticulol was closely associated with its antitumoral efficacy. Reticulol administered via the peritoneum of mice showed less metastasis inhibition than that injected intravenously. To demonstrate the mechanism for inhibition of metastasis, the inhibitory effect of reticulol for matrix metalloproteinase-2 or -9 involved in melanoma metastasis was investigated; however, they were not observed on zymogram gel. In addition, the antitumor efficacy of reticulol was not associated with cell cycle arrest or apoptosis. Therefore, it was inferred that reticulol known as a phosphodiesterase inhibitor directly inhibited the growth of B16F10 melanoma, showing necrotic response. These results suggest that reticulol protects its lung metastasis via the bloodstream by inhibiting the growth of B16F10 melanoma at the cellular level.

Taxonomy and Broad-Spectrum Antifungal Activity of Streptomyces sp. SCA3-4 Isolated From Rhizosphere Soil of Opuntia stricta

“…In addition, several members of the Actinobacterial taxa were also identified to produce a wide range of chemical compounds, including alkaloid, polyene macrolide, saccharide, pyrazoloisoquinolinone, butenolide, nucleoside, etc. These metabolites demonstrated significant biological activities such as antifungal, antitumor, antibacterial, anti-inflammatory, and enzyme inhibition (Lim et al, 2003; Bérdy, 2005; Feng et al, 2007).…”

Rhodium(III)‐Catalyzed Formal Cycloaddition between Thienopyridine/Thienopyrazine Carboxylic Acids and Alkynes, Triggered by C−H Activation

“…2 H ‐pyran‐2‐ones (ɑ‐pyrones) and 1 H ‐2‐benzopyran‐1‐ones (isocoumarins) are present in numerous natural [1] and synthetic [2] products that exhibit a wide range of biological activities such as antibacterial, [1a–c] anti‐fungal, [1a,d–h] antitumor, [1i–m,2a] anti‐inflammatory, [2b] anti‐diabetic, [1n] and anti‐HIV [1o–q] . Especially interesting are those derivatives exhibiting heterocyclic skeletons with sulfur and nitrogen atoms.…”

Isocoumarins: General Aspects and Recent Advances in their Synthesis

“…Similarly, imidazol‐1‐yl‐substituted 3,4‐dihydroisocoumarin is used as an aldosterone synthase inhibitor . Drugs containing the isocoumarin scaffold such as capillarin, arternidin, oosponol and oospolactone are used for fungal infections while cytogenin, reticulol and diaporthin are used as antitumor/antiarthritic agents and thunberginol A as well as thunberginol B are used as antimicrobial compounds (Figure ). Isocoumarins are also employed as key intermediates in the synthesis of a variety of complex heterocyclic compounds …”